PMID- 37799329 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231026 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 34 DP - 2023 Dec 12 TI - The decoy oligodeoxynucleotide against HIF-1alpha and STAT5 ameliorates atopic dermatitis-like mouse model. PG - 102036 LID - 10.1016/j.omtn.2023.102036 [doi] LID - 102036 AB - Atopic dermatitis (AD) is a common inflammatory skin disease caused by an immune disorder. Mast cells are known to be activated and granulated to maintain an allergic reaction, including rhinitis, asthma, and AD. Although hypoxia-inducible factor-1 alpha (HIF-1alpha) and signal transducer and activator of transcription 5 (STAT5) play crucial roles in mast cell survival and granulation, their effects need to be clarified in allergic disorders. Thus, we designed decoy oligodeoxynucleotide (ODN) synthetic DNA, without open ends, containing complementary sequences for HIF-1alpha and STAT5 to suppress the transcriptional activities of HIF-1alpha and STAT5. In this study, we demonstrated the effects of HIF-1alpha/STAT5 ODN using AD-like in vivo and in vitro models. The HIF-1alpha/STAT5 decoy ODN significantly alleviated cutaneous symptoms similar to AD, including morphology changes, immune cell infiltration, skin barrier dysfunction, and inflammatory response. In the AD model, it also inhibited mast cell infiltration and degranulation in skin tissue. These results suggest that the HIF-1alpha/STAT5 decoy ODN ameliorates the AD-like disorder and immunoglobulin E (IgE)-induced mast cell activation by disrupting HIF-1alpha/STAT5 signaling pathways. Taken together, these findings suggest the possibility of HIF-1alpha/STAT5 as therapeutic targets and their decoy ODN as a potential therapeutic tool for AD. CI - (c) 2023 The Authors. FAU - Gwon, Mi-Gyeong AU - Gwon MG AD - Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - Leem, Jaechan AU - Leem J AD - Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - An, Hyun-Jin AU - An HJ AD - Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - Gu, Hyemin AU - Gu H AD - Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - Bae, Seongjae AU - Bae S AD - Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - Kim, Jong Hyun AU - Kim JH AD - Department of Biochemistry, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. FAU - Park, Kwan-Kyu AU - Park KK AD - Department of Pathology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea. LA - eng PT - Journal Article DEP - 20230920 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC10550406 OTO - NOTNLM OT - HIF-1alpha OT - MT: Oligonucleotides: Therapies and Applications OT - STAT5 OT - atopic dermatitis OT - decoy oligodeoxynucleotide OT - mast cell COIS- The authors declare no competing interests. EDAT- 2023/10/06 06:43 MHDA- 2023/10/06 06:44 PMCR- 2023/09/20 CRDT- 2023/10/06 03:48 PHST- 2023/04/02 00:00 [received] PHST- 2023/09/15 00:00 [accepted] PHST- 2023/10/06 06:44 [medline] PHST- 2023/10/06 06:43 [pubmed] PHST- 2023/10/06 03:48 [entrez] PHST- 2023/09/20 00:00 [pmc-release] AID - S2162-2531(23)00254-8 [pii] AID - 102036 [pii] AID - 10.1016/j.omtn.2023.102036 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2023 Sep 20;34:102036. doi: 10.1016/j.omtn.2023.102036. eCollection 2023 Dec 12.